Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems.

Previous reports have shown the use of hydroxyapatite (HAp) and related calcium phosphate coatings on metal and nonmetal substrates for preparing tissue-engineering scaffolds, especially for osteogenic differentiation. These studies have revealed that the structural properties of coated substrates are dependent significantly on the method and conditions used for coating and also whether the substrates had been modified prior to the coating. In this article, we have done a comparative evaluation of the structural features of the HAp coatings, prepared by using simulated body fluid (SBF) at 25 degrees C for various time periods, on a nonporous metal substrate titanium-aluminium-vanadium (Ti-6Al-4V) alloy and a bioinert ceramic substrate alpha-alumina (alpha-Al(2)O(3)), with and without their prior treatment with the globular protein bovine serum albumin (BSA). Our analysis of these substrates by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectrometry showed significant and consistent differences in the quantitative and qualitative properties of the coatings. Interestingly, the bioactivity of these substrates in terms of supporting in vitro cell adhesion and spreading, and in vivo effects of implanted substrates, showed a predictable pattern, thus indicating that some coated substrates prepared under our conditions could be more suitable for biological/biomedical applications.

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Commercial-grade dense Ti-6Al-4V alloy substrate was mechanically roughened, cleaned, and treated with a globular protein [bovine serum albumin (BSA)] for 4 h. Biomimetic calcium phosphate (Ca-P) coating was applied onto the above-treated substrate by immersion into simulated body fluid (SBF) at 25 °C for a period of 4 days, with periodic replacement by freshly prepared SBF at 48-h intervals. After 4 days, branched micron-sized fibers of hydroxyapatite (HAp), resembling the structure of bone, were obtained, connecting the clusters of HAp crystal plates in the coating (thickness ∼200 μm) on the substrate surface. Structural and compositional characterization of the coating was carried out using field emission scanning electron microscopy (FE-SEM) with energy-dispersive x-ray analysis unit (EDX) facility, x-ray diffraction (XRD), and Fourier transform infrared (FTIR) data. In vitro cytotoxicity (ISO 10993-5, 1999), cell adhesion assays, and phase contrast microscopy were performed using NIH 3T3 fibroblast cell lines to ascertain the bioactivity of the coated substrates, with and without protein treatment. Based on our study, we propose a correlation between a specific physical structure of the HAp coating and its biological properties.

BackgroundAnchorage independent growth is an important hallmark of oncogenic transformation. Previous studies have shown that when adhesion dependent fibroblasts were prevented from adhering to a substrate they underwent anoikis. In the present study we have demonstrated how anoikis resistant cells gain the transformation related properties with sequential selection of genes. We have proposed this process as a model system for selection of transformed cells from normal cells.ResultsThis report demonstrates that some fibroblasts can survive during late stages of anoikis, at which time they exhibit transformation-associated properties such as in vitro colony formation in soft agar and in vivo subcutaneous tumour formation in nude mice. Cytogenetic characterisation of these cells revealed that they contained a t (2; 2) derivative chromosome and they have a selective survival advantage in non adherent conditions. Gene expression profile indicated that these cells over expressed genes related to hypoxia, glycolysis and tumor suppression/metastasis which could be helpful in their retaining a transformed phenotype.ConclusionOur results reveal some new links between anoikis and cell transformation and they provide a reproducible model system which can potentially be useful to study multistage cancer and to identify new targets for drug development.